Patients with head and neck squamous cell carcinoma (HNSCC) are at high risk for the development of metastatic carcinoma in the lung. Studies suggest that 5-15% of patients with HNSCC develop lung metastases (Ferlito, et al. (2001) ORL J. Otorhinolaryngol. Relat. Spec. 63:202-7). However, because patients with HNSCC are often heavy tobacco users, they are also at risk for second primary cancers, with squamous cell carcinoma of the lung (LSCC) being the most common (Jones, et al. (1995) Cancer 75:1343-53).
In some cases, the distinction between a lung metastasis and a second primary lung carcinoma can be distinguished on clinical grounds. The presence of multiple pulmonary nodules is usually considered evidence of metastatic disease. However, in subjects who present with a solitary lung nodule, the distinction between metastasis and primary carcinoma can be more problematic. Usually, patients with HNSCC who are found to have solitary pulmonary lesions undergo surgery or needle biopsy with pathologic evaluation. If the lung lesion is also of squamous cell histology, the distinction between metastasis and primary LSCC is extremely difficult. Currently this distinction is made by comparison of histological grade or by the presence of other premalignant changes in the respiratory epithelium; however, the accuracy of this approach is unclear.
Making the correct diagnosis has practical importance for choice of therapy. Although patients with either a primary LSCC or a solitary HNSCC metastases may be eligible for surgical resection, the surgical procedure (wedge resection versus lobectomy) and the use of adjuvant therapy is usually different in these situations. Additionally, patients with early stage LSCC have a significantly better prognosis than patients with metastatic HNSCC.
Recent gene expression studies have demonstrated the potential to classify the origin of human carcinomas cell lines (Nishizuka, et al. (2003) Cancer Res. 63:5243-50) and human tumors (Giordano, et al. (2001) Am. J. Pathol. 159:1231-8; Ramaswamy, et al. (2001) Proc. Natl. Acad. Sci. USA 98:15149-54). Although a number of studies have examined gene profiles in head and neck squamous cell carcinomas (Ginos, et al. (2004) Cancer Res. 64:55-63; Belbin, et al. (2002) Cancer Res. 62:1184-90) and lung squamous cell cancers (Borczuk, et al. (2003) Am. J. Pathol. 163:1949-60) with their tissues of origin, the patterns in these two types of tumors have only been compared in one previous study (Talbot, et al. (2005) Cancer Res. 65:3063-71). In this study, gene expression profiling was used to compare 21 lung cancer and 31 tongue cancer samples, wherein a distinction between HNSCC and LSCC tumors was achieved using hierarchical clustering with gene sets of 100-500 genes. The accuracy of these predictions decreased when the number of genes was reduced below 100.
Moreover, the use of genetic abnormalities has been suggested to distinguish between a primary lung tumor and pulmonary metastases. Paired tumors from 16 patients with HNSCC and a solitary lung nodule were compared for loss of heterozygosity on chromosomal arms 3p and 9p (Leong, et al. (1998) J. Natl. Cancer Inst. 90:972-7). The use of loss of heterozygosity distinguished 13 of the 16 cases as primary lung cancer or metastasis based on discordant versus concordant allelic patterns between the index tumor and the lung lesion. A separate study using loss of heterozygosity suggests that many squamous lung lesions in patients with HNSCC, that are currently classified as metastases based on clinical criteria, may in fact be primary lung cancers (Geurts, et al. (2005) Clin. Cancer Res. 11:6608-14). Although loss of heterozygosity is potentially useful, this technique is time consuming, not widely available, not completely accurate, and most importantly, requires appropriate tissue from both the primary and the lung lesion.
Needed in the art is a reliable method for distinguishing between primary and metastatic squamous cell carcinoma of the lung using a small number of differentially expressed genes. The present invention meets this long-felt need in the art.